Neural information on the state of bladder filling is fundamental to successful storage and emptying operations in the urinary bladder. Increased bladder pressure excites small, myelinated mechanoreceptive Aomega fibers in the pelvic nerves and unmyelinated c-fibers, that we have identified as chemoreceptors, in the hypogastric and, possibly, the pelvic nerves. Both are excited by bladder filling but the myelinated fibers respond at lower pressures than the unmyelinated fibers. Filling cystometrograms in conscious rats will be incorporated with neurophysiologic recordings of multiunit and single unit activity from bladder afferent nerves to evaluate the extent to which these unmyelinated chemoreceptive fibers participate in normal and irritative bladder function. Specifically, we will also investigate if chemoreceptive fibers can become sensitized to produce irritative disorders of the urinary tract, such as interstitial cystitis (IC), an irritative bladder disorder of unknown etiology that is classically described most frequently in the middle-aged female. A deficient glycosaminoglycans (GAG) layer has been proposed as a factor in the etiology of interstitial cystitis and cystometric and electrophysiological recording techniques will be used to test the importance of the GAG layer as a permeability barrier which protects chemoreceptive nerves from exposure to the irritant action of urine. In view of the reported efficacy of intravesical instillation of dimethyl sulfoxide (DMSO) in the alleviation of the discomfort of this disorder, the actions of DMSO on the responsiveness of bladder afferent fibers will be investigated for the first time. An important issue in the understanding the pain of IC is whether fibers which mediate irritative symptoms from the bladder are also active during normal bladder function. It is reported that unmyelinated fibers are insensitive to bladder filling with isotonic saline at physiologic intravesical pressures unless first sensitized by inflammation, implicating them as nociceptors mediating pain from an inflamed bladder. However, bladder filling with isotonic saline is an inappropriate stimulus for these nerves. Our preliminary studies have identified them as chemoreceptive afferents which are excited when the bladder is filled at physiologic pressures with solutions of KC1 at concentrations found in normal urine (100-200 mM). We propose that unmyelinated chemoreceptive fibers are active at normal intravesical pressures and convey a sense of bladder fullness at high intravesical volumes. However, more intense activation contributes to the pain and burning associated with irritative bladder disorders.